An extracellular matrix, consisting of collagen, fibronectin, laminin, proteoglycan, etc., has a function to support tissues, and plays a role in propagation, differentiation, adhesion, or the like in cells. Metalloproteinases which are protease having a metal ion in the active center, especially matrix metalloproteinases (MMP), are concerned with the degradation of the extracellular matrix. Many types of MMP, from MMP-1 (collagenase type I) to MMP-23, have been reported as enzymes working for the growth, remodeling of tissues, etc. under usual physiological conditions. It is reported, however, that the progression of various kinds of diseases involving breakdown and fibrosis of tissues (e.g., osteoarthritis, rheumatoid arthritis, corneal ulceration, periodontitis, metastasis and invasion of tumor, and virus infection (HIV infection)) is related with increase of the manifestation or activity of the above-mentioned enzyme.
Matrix metalloproteinases-12 (MMP-12) is produced from macrophage and has a character which decomposes elastin and is different from other MMPs'. It is known that this enzyme cleaves collagen type I, collagen type IV, fibronectin, laminin and the like. It is also described in SCIENCE 1997, 277(26), 2002-2004 and Exp. Opin. Ther. Patents(1999) 9(7),851-895 and the like that MMP-12 plays a role in pulmonary emphysema. Therefore, MMP-12 is considered to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD) which is characterized by respiratory obstruction caused by pulmonary emphysema or chronic bronchitis. It is suggested in Exp. Opin. Ther. Patents (1999) 9(7),851-895 and the like that MMP-12 relates to diseases of metastatic carcinoma, atherosclerosis and the like.
Sulfonamide derivatives having an inhibitory activity against, MMP are described in WO97/27174, WO99/04780 and the like.
No compound having an inhibitory activity against MMP-12 is known.